Chronic renal insufficiency, such as occurs in association with the later stages of many pathological processes in the kidney, is characterized by a complex suppression of immune responses. This immunosuppression may be a serious threat and complicate the care and management of patients with chronic renal insufficiency. Therefore a better understanding of the mechanism of the pathological suppression of immune responses in uremia ought to provide a rational basis for the improved treatment and management of these patients. It is the objective of this study to isolate and characterize biochemically the macromoleclar inhibitor of the mixed lymphocyte reaction (MLR) present in the serum of inbred rats which have been made uremic by subtotal nephrectomy. Serum will be fractionated by biochemical methods and the isolated fractions will be assayed in the MLR for inhibitory activity. The biologically active fractions will be analyzed biochemically. The immunosuppressive factor containing fractions will also be studied immunochemically. A radioimmune assay for such immunosuppressive material will be developed if its reactivity is distinct. When the immunosuppressive factor (or factors) has been sufficiently purified, its mechanism of action will be studied in detail in vitro and in vivo. The biochemical characterization of the MLR-inhibitory factor present in the serum of uremic rats will be made the basis of a similar and comparative study of individual serum samples from selected uremic human patients.